Based on the success of the initial 10-year award, the ultimate goals of this COBRE renewal application are to complete the establishment at Dartmouth of a nationally recognized Center for Molecular, Cellular, and Translational Immunological Research, and to transition this COBRE Center for Immunological Research (COBRE-CIR) to an infrastructure-based, freestanding (from COBRE funding), sustainable center in five years. With the foundation of a long-standing Immunology Program, which has now been substantially enhanced by COBRE support, this proposal takes advantage of a highly interactive core of collaborative faculty at Dartmouth Medical School (DMS) and Dartmouth Hitchcock Medical Center (DHMC). With this expanded investigator base, a Phase III COBRE award will provide the resources to build the needed infrastructure to sustain the COBRE-CIR, further grow the Program, and facilitate inter-disciplinary basic science to translational immunological research. This infrastructure will include the continued mentored development of our immunological faculty, especially those investigators previously supported by COBRE;expansion of the COBRE Cores and their full integration with existing complementary cores and shared services at DMS/DHMC, particularly the Norris Cotton Cancer Center and the other Immunology and "Lung Biology" COBREs at Dartmouth and the University of Vermont;and an enhanced Pilot Project Program with targeting to mentored, collaborative, and/or translational/human systems research. Together with substantive Institutional commitment by DMS/DHMC, there is confidence that the strong existing cadre of investigators, already expanded and matured by the COBRE mechanism, can be further developed to complete the formation of a sustainable Center for Immunological Research that is grounded in excellent basic science investigation, embraces a translational approach to promote bidirectional bench-to-bedside application of hypothesis-driven research, and has a regional, if not also national, impact.